Antibacterial coaxial hydro-membranes accelerate diabetic wound healing by tuning surface immunomodulatory functions

Wei Zhang; Sizhan Xia; Tingting Weng; Min Yang; Jiaming Shao; Manjia Zhang; Jialiang Wang; Pengqing Xu; Jintao Wei; Ronghua Jin; Meirong Yu; Zhongtao Zhang; Chunmao Han; Xingang Wang

doi:10.1016/j.mtbio.2022.100395

Antibacterial coaxial hydro-membranes accelerate diabetic wound healing by tuning surface immunomodulatory functions

Mater Today Bio. 2022 Aug 13:16:100395. doi: 10.1016/j.mtbio.2022.100395. eCollection 2022 Dec.

Authors

Wei Zhang^{1

2}, Sizhan Xia^{1

2}, Tingting Weng^{1

2}, Min Yang^{1

2}, Jiaming Shao^{1

2}, Manjia Zhang³, Jialiang Wang^{1

2}, Pengqing Xu^{1

2}, Jintao Wei^{2

4

5

6}, Ronghua Jin^{1

2}, Meirong Yu², Zhongtao Zhang^{1

2}, Chunmao Han^{1

2}, Xingang Wang^{1

2}

Affiliations

¹ Department of Burns and Wound Care Center, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, 310000, China.
² The Key Laboratory of the Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Hangzhou 310000, China.
³ The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
⁴ Department of Emergency Medicine, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, 310000, China.
⁵ Institute of Emergency Medicine, Zhejiang University, Hangzhou, 310000, China.
⁶ Zhejiang Province Clinical Research Center for Emergency and Critical Care Medicine, Jiefang Road 88, Hangzhou, 310009, China.

Abstract

Diabetic foot ulcers, typical non-healing wounds, represent a severe clinical problem. Advanced glycation end-products (AGEs), which create a prolonged pro-inflammatory micro-environment in defective sites, can be responsible for refractoriness of these ulcers. Macrophages are polarized to the M2 phenotype to facilitate the transition from a pro-inflammatory microenvironment to an anti-inflammatory microenvironment, which has been demonstrated to be an effective way to accelerate diabetic wound closure. Herein, we developed coaxial hydro-membranes mimicking the extracellular matrix structure that are capable of anti-inflammatory and antibacterial functions for diabetic wound repair. These fibrous membranes maintain a moist microenvironment to support cell proliferation. Macrophages grow in an elongated shape on the surface of the fibrous membranes. The fibrous membranes effectively impaired macrophage AGE-induced M1 polarization and induced macrophage polarization towards the M2 phenotype. The effects of the fibrous membranes on the interactions between macrophages and repair cells under a diabetic condition were also investigated. Furthermore, in vivo results from a full-thickness diabetic wound model confirmed the potential of the coaxial hydro-membranes to accelerate wound healing. This study's results indicate that the developed bioactive anti-inflammatory and antibacterial wound dressing can affect AGE-induced macrophage activation and crosstalk between macrophages and fibroblasts for treating diabetic wounds.

Keywords: Advanced glycation end products; Anti-inflammatory activity; Diabetic wound healing; Immunomodulatory biomaterials; Macrophage polarization.